Rates and consequences of posttraumatic distress among American Indian adults with type 2 diabetes.
This study examined the prevalence of screened posttraumatic stress disorder (PTSD) and associated diabetes-related outcomes. A sample of American Indian adults with type 2 diabetes (n = 218) participated in interviewer-administered surveys. Using a cutoff of 3 on the Primary Care PTSD screener, 21.8 % of participants screened positive for PTSD. PTSD symptoms were negatively associated with self-rated health status and positively associated with past year hospitalization after controlling for several demographic factors, but not after controlling for depressive symptoms. Past month frequency of hyperglycemia symptoms was not related to PTSD symptoms. When grouped by mental health conditions (neither screened PTSD nor depressive symptoms, screened PTSD only, depressive symptoms only, and both), those with both screened PTSD and depressive symptoms reported the highest proportion of any past month hyperglycemia, past year hospitalization, and low self-rated health status. Screened PTSD, especially in those with comorbid depressive symptoms, is an important consideration in diabetes care.


Examining the social porosity of environmental features on neighborhood sociability and attachment.
The local neighborhood forms an integral part of our lives. It provides the context through which social networks are nurtured and the foundation from which a sense of attachment and cohesion with fellow residents can be established. Whereas much of the previous research has examined the role of social and demographic characteristic in relation to the level of neighboring and cohesion, this paper explores whether particular environmental features in the neighborhood affect social porosity. We define social porosity as the degree to which social ties flow over the surface of a neighborhood. The focus of our paper is to examine the extent to which a neighborhood's environmental features impede the level of social porosity present among residents. To do this, we integrate data from the census, topographic databases and a 2010 survey of 4,351 residents from 146 neighborhoods in Australia. The study introduces the concepts of wedges and social holes. The presence of two sources of wedges is measured: rivers and highways. The presence of two sources of social holes is measured: parks and industrial areas. Borrowing from the geography literature, several measures are constructed to capture how these features collectively carve up the physical environment of neighborhoods. We then consider how this influences residents' neighboring behavior, their level of attachment to the neighborhood and their sense of neighborhood cohesion. We find that the distance of a neighborhood to one form of social hole-industrial areas-has a particularly strong negative effect on all three dependent variables. The presence of the other form of social hole-parks-has a weaker negative effect. Neighborhood wedges also impact social interaction. Both the length of a river and the number of highway fragments in a neighborhood has a consistent negative effect on neighboring, attachment and cohesion.


Identifies Immune Feature Genes for Prediction of Chemotherapy Benefit in Cancer.
Chemotherapy is still the most fundamental treatment for advanced cancers so far. Previous studies have indicated that immune cell infiltration (ICI) index could serve as a biomarker to predict chemotherapy benefit in breast cancer and colorectal cancer. However, due to different responses of tumor infiltrating immune cells (TIICs) to chemotherapy, the prediction efficiency of ICI index is not fully confirmed by now. In our study, we first extended this conclusion in 7 cancers that high ICI index could certainly indicate chemotherapy benefit (P<0.05). But we also found the fraction of different TIICs and the interaction of TIICs were varies greatly from cancer to cancer. Therefore, we executed correlation and causal network analysis to identify chemotherapy associated immune feature genes, and fortunately identified six co-owned immune feature genes (CD48, GPR65, C3AR1, CD2, CD3E and ARHGAP9) in 10 cancers (BLCA, BRCA, COAD, LUAD, LUSC, OV, PAAD, SKCM, STAD and UCEC). Base on this, we developed a chemotherapy benefit prediction model within six co-owned immune feature genes through random forest classifying (AUC =0.83) in cancers mentioned above, and validated its efficiency in external datasets. In short, our work offers a novel model with a shrinking panel which has the potential to guide optimal chemotherapy in cancer.


Only one of three hydrophobins (Hyd1-3) contributes to conidial hydrophobicity and insect pathogenicity of Metarhizium robertsii.
Class I/II hydrophobins constitute a family of small amphiphilic proteins that mediate cell hydrophobicity and adhesion to host or substrata and have pleiotropic effects in filamentous fungi. Here we report that only class I Hyd1 is essential for conidial hydrophobicity and insect pathogenicity among three hydrophobins (Hyd1-3) characterized in Metarhizium robertsii, an insect-pathogenic fungus. Aerial conidiation levels of three Δhyd1 mutants were much more reduced in 5-day-old cultures than in 7-day-old cultures, which were wettable (hydrophilic), but restored to a wild-type level in 15-day-old cultures. The Δhyd1 mutants were compromised in conidial quality, including significant decreases in hydrophobicity (58%), adhesion to insect cuticle (36%), insect pathogenicity via normal cuticle infection (37%), UVB resistance (20%), and heat tolerance (10%). In contrast, none of all examined phenotypes were affected in the null mutants of hyd2 and hyd3. Intriguingly, micromorphology and integrity of hydrophobin rodlet bundles on conidial coat were not affected in all mutant and wild-type strains, but the rodlet bundles were disordered in the absence of hyd1, suggesting a link of the disorder to the decreased hydrophobicity. Therefore, Hyd1 mediates the fungal hydrophobicity and plays an important role in conidial quality control and insect-pathogenic lifecycle. Class I Hyd2 and class II Hyd3 seem functionally redundant in M. robertsii.


Influences of dietary and environmental stress on microbial populations in the murine gastrointestinal tract.
Aerobic and anaerobic cultural techniques and histological methods were used in a study of the effects of environmental and dietary stress on the indigenous microbiota of the gastrointestinal tract of mice. Mice previously inoculated with Salmonella typhimurium were examined in a similar manner. Three strains of mice (CD-1, Ha/ICr, and C57BL) were used. Control animals previously inoculated with S. typhimurium had low population levels of Salmonella bacteria in the small and large bowel. Mice previously inoculated with Salmonella and then deprived of food, water, and bedding for 48 h harbored high population levels of these bacteria in their small and large bowels. Coliforms increased in numbers in the large bowel of stressed mice inoculated with Salmonella and in the jejunum-ileum and cecum of stressed mice not previously inoculated with Salmonella. Control mice had high population levels of lactobacilli inhabiting the keratinized squamous epithelium of the stomach. Stressed mice showed dramatic reductions in these populations of lactobacilli. Populations of fusiform-shaped bacteria associated with the mucosal epithelium of the cecum and colon in control mice were reduced in stressed mice as determined by microscope examination of histological sections. Total anaerobic counts were similar, however, in both stressed and control animals. Environmental and dietary stress markedly alter the gastrointestinal microbiota in mice. Therefore, such stressful conditions profoundly affect the factors that regulate the localization and population levels of microorganisms in the stomach and intestines.


Graded activation in frog muscle fibers.
The membrane potential of frog single muscle fibers in solutions containing tetrodotoxin was controlled with a two-electrode voltage clamp. Local contractions elicited by 100-ms square steps of depolarization were observed microscopically and recorded on cinefilm. The absence of myofibrillar folding with shortening to striation spacings below 1.95 microm served as a criterion for activation of the entire fiber cross section. With depolarizing steps of increasing magnitude, shortening occurred first in the most superficial myofibrils and spread inward to involve axial myofibrils as the depolarization was increased. In contractions in which the entire fiber cross section shortened actively, both the extent of shortening and the velocity of shortening at a given striation spacing could be graded by varying the magnitude of the depolarization step. The results provide evidence that the degree of activation of individual myofibrils can be graded with membrane depolarization.


Photoreductive Elimination of Chlorine from Antimony in an [SbPd]VII Complex.
As part of our ongoing interest in main group species that support the photoreductive elimination of halogens, we have synthesized [Cl3SbVPdIICl2(o-dppp)2] (o-dppp = o-(Ph2P)C6H4), a palladium dichloride complex featuring a Lewis acidic trichlorostiborane moiety positioned within the ligand architecture. Upon UV irradiation, this complex undergoes a clean photoreductive chlorine elimination reaction which produces [Cl2SbIVPdICl(o-dppp)2], a complex with a covalent Sb-Pd bond. This transformation illustrates the viability of antimony as an element from which a halogen can be photoeliminated; it also shows that a metal halide can be photolytically coupled with a main group halide to generate a metal-element bond.


Do informed consent documents for cancer trials do what they should? A study of manifest and latent functions.
Though patient information leaflets (PILs) are provided to those invited to take part in medical research, they usually fall short in facilitating informed decisions about participation. We aimed to explore why there is an enduring requirement for a process that seems not to 'work', and to explain why the problems have proven resistant to correction. We analysed applications for ethical approval for 13 oncology trials and related official guidance. We interviewed 26 patients invited to participate in the trials. Data analysis was based on the constant comparative method. We show that PILs function latently to satisfy purposes other than their manifest function as a decision-facilitating tool. PILs are the outcome of a process of institutional scripting that is strongly shaped by the accountability demands inherent in the ethical review process. This results in the PIL being made to serve purposes both as a prospectus and as a contract. Though PILs have value for some patients, most do not recognise these documents as operating primarily in their interests. Patients make decisions in ways that deviate from official ideals. This analysis is important in recognising that no simple technical fix is available, and in enhancing sociological understanding of the institutional role of documents.


[Dopamine amides with essential or fundamental fatty acids. Synthesis and pharmacological study].
Dopamine amides with palmitic, stearic and linoleic acid, their diacetates and carbonates were synthesized and their action on mice and rats was studied. The experimental results which are obtained from these derivatives (antagonized or non antagonized hypomotility by neuroleptics in low doses on mice, potentiation of the haloperidol catalepsy or not, on rats) could be compatible with a selective action of these amides on the autoreceptors of the cerebral dopaminergic neurons and with a preferential activity of some derivatives on certain cerebral areas (mesencephalon or striatum).


The surveillance complex interacts with the translation release factors to enhance termination and degrade aberrant mRNAs.
The nonsense-mediated mRNA decay pathway is an example of an evolutionarily conserved surveillance pathway that rids the cell of transcripts that contain nonsense mutations. The product of the UPF1 gene is a necessary component of the putative surveillance complex that recognizes and degrades aberrant mRNAs. Recent results indicate that the Upf1p also enhances translation termination at a nonsense codon. The results presented here demonstrate that the yeast and human forms of the Upf1p interact with both eukaryotic translation termination factors eRF1 and eRF3. Consistent with Upf1p interacting with the eRFs, the Upf1p is found in the prion-like aggregates that contain eRF1 and eRF3 observed in yeast [PSI+] strains. These results suggest that interaction of the Upf1p with the peptidyl release factors may be a key event in the assembly of the putative surveillance complex that enhances translation termination, monitors whether termination has occurred prematurely, and promotes degradation of aberrant transcripts.


Epidemiology of free-living amoebae infections in Africa: a review.
FLA-related conditions are a rare medical occurrence. Despite their rarity, they are considered a public health concern for two reasons: the absence of a regular treatment regimen in the case of central nervous system infections and the fast progression of the symptoms leading to fatal outcomes. A total of 358 articles were retrieved from different databases (91 from PubMed, 26 from NCBI, 138 from Academia, 102 from Science Direct, and one from IJMED). 7 (46.6%) clinical cases came from Egypt, 2 (13.3%) cases of FLA infection came from Nigeria, 3 (20%) cases came from the Gambia, and 1 (6.6%) case was reported from African countries like Algeria, Tunisia, South Africa, and Zambia. Medical conditions caused by free-living amoeba are considered significant public health concerns. These ubiquitous organisms can cause both fatal and debilitating health conditions. Immediate diagnosis of cases and proper hygienic practices are necessary to provide direct medical intervention. They may be the key to reducing the morbidity and mortality rates from FLA-acquired infections. Although several government-led initiatives have been implemented to mitigate a plethora of parasitic diseases, the case of FLA-related conditions in African countries has yet to be realized.


TDP-43 and FUS en route from the nucleus to the cytoplasm.
Misfolded or mislocalized RNA-binding proteins (RBPs) and, consequently, altered mRNA processing, can cause neuronal dysfunction, eventually leading to neurodegeneration. Two prominent examples are the RBPs TAR DNA-binding protein of 43 kDa (TDP-43) and fused in sarcoma (FUS), which form pathological messenger ribonucleoprotein aggregates in patients suffering from amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two devastating neurodegenerative disorders. Here, we review the multiple functions of TDP-43 and FUS in mRNA processing, both in the nucleus and in the cytoplasm. We discuss how TDP-43 and FUS may exit the nucleus and how defects in both nuclear and cytosolic mRNA processing events, and possibly nuclear export defects, may contribute to neurodegeneration and ALS/FTD pathogenesis.


Cost-effectiveness of cardiac biomarkers as screening test in acute chest pain.
Acute chest pain is an important and frequently occurring symptom in patients. Chest pain is often a sign of ischemic heart disease. Associated findings of electrocardiograph (ECG) are rather heterogeneous, and traditional cardiac biomarkers such as Creatine Kinase-MB (CK-MB) suffer from low cardiac specificity and sensitivity. In this study cost effectiveness of cardiac biomarkers single quantitative measurement was examined. The present descriptive-analytic study conducted on patients who were asked for troponin I and CK-MB. All patients who referred to Emergency unit of Tabriz Imam Reza educational-medical center during January 2012 to July the 2013 were included in study. All patients included in the study were documented in terms of age, sex, working shift of referring, main complaint of patient, symptoms in referring, ECG findings, and results of troponin I and CK-MB tests. In this study, 2900 patients were studied including 1440 (49.7%) males and 1460 (50.3%) females. Mean age of patients was 62.91 (SD=14.36). Of all patients 1880 (64.8%) of patients referred during 8 a.m. to 8 p.m. and 1020 (35.2%) patients were referred during 8 p.m. to 8 a.m. The sensitivity of cardiac biomarkers' test in diagnosing Acute Coronary Syndrome (ACS) disease was calculated as 44.8% and its specificity was 86.6%. For diagnosing Acute Myocardial Infarction (AMI), sensitivity of cardiac biomarkers' test was 72.2% and its specificity was 86%. None of patients who were finally underwent unstable angina diagnosis showed increase in cardiac enzymes. In conclusion, cardiac biomarkers can be used for screening acute chest pains, also cost effectiveness of cardiac biomarkers, appropriate specificity and sensitivity can guarantee their usefulness in emergency room.


Rodent versus human insulitis: why the huge disconnect?
The purpose of this article is to summarize recent developments in the histopathology of recent-onset type 1 diabetes. Insulitis is considered to be the defining lesion in young type 1 diabetic patients, and insight into its pathogenic mechanism is crucial for the development of effective new therapies. The present overview highlights some recent developments including an international consensus guideline for the diagnosis of insulitis in type 1 diabetic patients, immunophenotyping of the insulitic lesions, evidence for a heterogeneity of the disease process and a discussion on the differences and similarities between insulitis in patients and in rodent models of the disease. We have reviewed recent data, published over the last year, on the nature and mechanism of insulitis in both patients and the nonobese diabetic mouse model.


A review of transfusion practice before, during, and after hematopoietic progenitor cell transplantation.
The increased use of hematopoietic progenitor cell (HPC) transplantation has implications and consequences for transfusion services: not only in hospitals where HPC transplantations are performed, but also in hospitals that do not perform HPC transplantations but manage patients before or after transplantation. Candidates for HPC transplantation have specific and specialized transfusion requirements before, during, and after transplantation that are necessary to avert the adverse consequences of alloimmunization to human leukocyte antigens, immunohematologic consequences of ABO-mismatched transplantations, or immunosuppression. Decisions concerning blood transfusions during any of these times may compromise the outcome of an otherwise successful transplantation. Years after an HPC transplantation, and even during clinical remission, recipients may continue to be immunosuppressed and may have critically important, special transfusion requirements. Without a thorough understanding of these special requirements, provision of compatible blood components may be delayed and often urgent transfusion needs prohibit appropriate consultation with the patient's transplantation specialist. To optimize the relevance of issues and communication between clinical hematologists, transplantation physicians, and transfusion medicine physicians, the data and opinions presented in this review are organized by sequence of patient presentation, namely, before, during, and after transplantation.


Experiences of occupational therapists returning to work after maternity leave.
Returning to work after maternity leave can be a challenging, anxious and fraught experience for women, and has been portrayed in the literature as a generally negative experience. Interestingly, although occupational therapists were predominantly women, no research was found focussing on their experiences of returning to work after maternity leave. The aim of this research was to gain an insight into occupational therapists' experiences of returning to work following maternity leave. Principles of interpretive phenomenological analysis were used to explore the individual experiences of six Australian occupational therapists returning to work after a period of maternity leave. Individual semi-structured interviews lasting up to 90 minutes were conducted. Interviews were audio-recorded, transcribed and then analysed. Two major themes emerged from the analysis of interviews: compromise and feeling valued. The experience of returning to work was a process of compromise in which women found strategies to cope with their changing roles and demands, to find a balance between home and work life. The women wanted to feel valued by their managers and co-workers, as this enabled them to feel comfortable and confident with some of the compromises they made. Occupational therapists returning to work after maternity leave will make compromises so that they can balance their home and work life. Occupational therapists value managers and co-workers who understand the compromises women make when returning to work following maternity leave and who create a supportive workplace that acknowledges and values their contribution.


Transjugular intrahepatic portosystemic stent shunt for medically refractory hepatic hydrothorax: A systematic review and cumulative meta-analysis.
To assess the effectiveness of transjugular intrahepatic portosystemic stent shunt (TIPSS) in refractory hepatic hydrothorax (RHH) in a systematic review and cumulative meta-analysis. A comprehensive literature search was conducted on MEDLINE, EMBASE, and PubMed covering the period from January 1970 to August 2014. Two authors independently selected and abstracted data from eligible studies. Data were summarized using a random-effects model. Heterogeneity was assessed using the I (2) test. Six studies involving a total of 198 patients were included in the analysis. The mean (SD) age of patients was 56 (1.8) years. Most patients (56.9%) had Child-Turcott-Pugh class C disease. The mean duration of follow-up was 10 mo (range, 5.7-16 mo). Response to TIPSS was complete in 55.8% (95%CI: 44.7%-66.9%), partial in 17.6% (95%CI: 10.9%-24.2%), and absent in 21.2% (95%CI: 14.2%-28.3%). The mean change in hepatic venous pressure gradient post-TIPSS was 12.7 mmHg. The incidence of TIPSS-related encephalopathy was 11.7% (95%CI: 6.3%-17.2%), and the 45-d mortality was 17.7% (95%CI: 11.34%-24.13%). TIPSS is associated with a clinically relevant response in RHH. TIPSS should be considered early in these patients, given its poor prognosis.


Vitamin C Supplementation in Healthy Individuals Leads to Shifts of Bacterial Populations in the Gut-A Pilot Study.
Gut microbes are crucial to human health, but microbial composition is often disturbed in a number of human diseases. Accumulating evidence points to nutritional modulation of the gut microbiota as a potentially beneficial therapeutic strategy. Vitamin C (ascorbic acid) may be of particular interest as it has known antioxidant and anti-inflammatory properties. In this study, we investigated whether supplementation with high-dose vitamin C may favourably affect the composition of the gut microbiota. In this pilot study, healthy human participants received 1000 mg vitamin C supplementation daily for two weeks. Gut microbiota composition was analysed before and after intervention by performing faecal 16S rRNA gene sequencing. In total, 14 healthy participants were included. Daily supplementation of high-dose vitamin C led to an increase in the relative abundances of Lachnospiraceae (p < 0.05), whereas decreases were observed for Bacteroidetes (p < 0.01), Enterococci (p < 0.01) and Gemmiger formicilis (p < 0.05). In addition, trends for bacterial shifts were observed for Blautia (increase) and Streptococcus thermophilus (decrease). High-dose vitamin C supplementation for two weeks shows microbiota-modulating effects in healthy individuals, with several beneficial shifts of bacterial populations. This may be relevant as these bacteria have anti-inflammatory properties and strongly associate with gut health.


Structurofunctional resting-state networks correlate with motor function in chronic stroke.
Motor function and recovery after stroke likely rely directly on the residual anatomical connections in the brain and its resting-state functional connectivity. Both structural and functional properties of cortical networks after stroke are revealed using multimodal magnetic resonance imaging (MRI). Specifically, functional connectivity MRI (fcMRI) can extract functional networks of the brain at rest, while structural connectivity can be estimated from white matter fiber orientations measured with high angular-resolution diffusion imaging (HARDI). A model that marries these two techniques may be the key to understanding functional recovery after stroke. In this study, a novel set of voxel-level measures of structurofunctional correlations (SFC) was developed and tested in a group of chronic stroke subjects. A fully automated method is presented for modeling the structure-function relationship of brain connectivity in individuals with stroke. Brains from ten chronic stroke subjects and nine age-matched controls were imaged with a structural T1-weighted scan, resting-state fMRI, and HARDI. Each subject's T1-weighted image was nonlinearly registered to a T1-weighted 152-brain MNI template using a local histogram-matching technique that alleviates distortions caused by brain lesions. Fractional anisotropy maps and mean BOLD images of each subject were separately registered to the individual's T1-weighted image using affine transformations. White matter fiber orientations within each voxel were estimated with the q-ball model, which approximates the orientation distribution function (ODF) from the diffusion-weighted measurements. Deterministic q-ball tractography was performed in order to obtain a set of fiber trajectories. The new structurofunctional correlation method assigns each voxel a new BOLD time course based on a summation of its structural connections with a common fiber length interval. Then, the voxel's original time-course was correlated with this fiber-distance BOLD signal to derive a novel structurofunctional correlation coefficient. These steps were repeated for eight fiber distance intervals, and the maximum of these correlations was used to define an intrinsic structurofunctional correlation (iSFC) index. A network-based SFC map (nSFC) was also developed in order to enhance resting-state functional networks derived from conventional functional connectivity analyses. iSFC and nSFC maps were individually compared between stroke subjects and controls using a voxel-based two-tailed Student's t-test (alpha = 0.01). A linear regression was also performed between the SFC metrics and the Box and Blocks Score, a clinical measure of arm motor function. Significant decreases (p < 0.01) in iSFC were found in stroke subjects within functional hubs of the brain, including the precuneus, prefrontal cortex, posterior parietal cortex, and cingulate gyrus. Many of these differences were significantly correlated with the Box and Blocks Score. The nSFC maps of prefrontal networks in control subjects revealed localized increases within the cerebellum, and these enhancements were diminished in stroke subjects. This finding was further supported by a reduction in functional connectivity between the prefrontal cortex and cerebellum. Default-mode network nSFC maps were higher in the contralesional hemisphere of lower-functioning stroke subjects. The results demonstrate that changes after a stroke in both intrinsic and network-based structurofunctional correlations at rest are correlated with motor function, underscoring the importance of residual structural connectivity in cortical networks.


Postprandial triglyceride response in visceral obesity in men.
Although metabolic disturbances are often observed in obese patients, increased accumulation of visceral adipose tissue (AT) has been shown to be more closely associated with high fasting triglyceride (TG) and insulin levels as well as with low HDL cholesterol concentrations than with excess body fatness per se. Interestingly, the fasting concentration of plasma TGs has been shown to be an important determinant of the magnitude and duration of the postprandial TG response. Yet little is known about the respective contributions of obesity versus excess visceral AT to the variation in postprandial TG clearance. In the present study, we examined potential differences in postprandial triglyceride-rich lipoprotein (TRL) responses in subjects characterized by high versus low levels of visceral AT. In a sample of 43 men (mean age: 41.3 +/- 9.6 years), we found that both excess body fat and visceral obesity were associated with increased postprandial TG responses in total TRL (r = 0.33-0.45). We also found a strong relationship between fasting plasma TG levels and postprandial total TRL-TG concentrations (r = 0.79, P < 0.0001). When matched for total body fat mass, individuals with high levels of visceral AT (> or =130 cm2; n = 10) as assessed by computed tomography were characterized by increased medium- and small-TRL-TG responses (P < 0.05) compared with subjects with low visceral AT accumulation (<130 cm2; n = 10). Moreover, this elevated response of small-TRL triglycerides noted in men with high levels of visceral AT was not accompanied by a concomitant increased retinyl palmitate response in this TRL fraction, suggesting that visceral obesity in men is accompanied by higher postprandial VLDL production than is found in obese men with lower levels of visceral AT. Increased postprandial insulin and free fatty acid (FFA) responses were also noted in men with high levels of visceral AT. Finally, postheparin plasma lipoprotein lipase activity was negatively correlated with the total-TRL-TG response in a subsample of 32 individuals (r = -0.37, P < 0.05). The results of the present study suggest that visceral obesity is associated with an impaired postprandial TG clearance. Furthermore, the exaggerated postprandial FFA response observed in subjects with high visceral AT suggests that visceral obesity may contribute to fasting and postprandial hypertriglyceridemia by altering FFA metabolism in the postprandial state.


Insight into the electronic and mechanical properties of novel TMCrSi ternary silicides from first-principles calculations.
Transition metal silicides (TMSis) are attractive advanced functional materials due to their low electronic resistivity, high melting-point, excellent mechanical properties and thermal stability. However, the overall performances of binary silicides are not satisfactory enough to meet the requirements of many commercial applications. To overcome this problem, utilizing ternary silicide is a good path to adjust the balance between the overall performances because metallic bond plays a key role in electronic properties. The TM-Si bond enhances the strength, while the alloying element (Cr) can effectively improve the oxidation and corrosion resistances. Therefore, we report the results of electronic, mechanical and thermodynamic properties of stable TMCrSi ternary silicides by using first-principles calculations. First, we found that TMCrSi ternary silicides are dynamically stable based on the phonon dispersion curves. Second, the constructed ternary silicides exhibit better electronic properties because of the formation of TM-Cr metallic bond. Importantly, these ternary silicides not only show high strength, but also have better ductility. Additionally, the Debye temperature and heat capacity of TMCrSi ternary silicides are discussed. Finally, through our study, we propose that TMCrSi ternary silicides are promising functional materials with potential applications in aerospace, microelectronic and energy storage systems.


Transient kinetics of a cGMP-dependent cGMP-specific phosphodiesterase from Dictyostelium discoideum.
Chemotactic stimulation of Dictyostelium discoideum cells induces a fast transient increase of cGMP levels which reach a peak at 10 s. Prestimulation levels are recovered in approximately 30 s, which is achieved mainly by the action of a guanosine 3',5'-monophosphate cGMP-specific phosphodiesterase. This enzyme is activated about fourfold by low cGMP concentrations. The phosphodiesterase has two distinct cGMP-binding sites: a catalytic site and an activator site. cAMP does not bind to either site; inosine 3',5'-monophosphate (cIMP) binds only to the catalytic site, whereas 8-bromoguanosine 3',5'-monophosphate (c-b8-GMP) preferentially binds to the activator site. For detailed kinetical measurements we have used [3H]cIMP as the substrate and c-b8-GMP as the activator. c-b8-GMP activated the hydrolysis of [3H]cIMP by reducing the Km, whereas the Vmax was not altered. The hydrolysis of [3H]cIMP was measured at 5-s intervals by using a new method for the separation of 5'-nucleotides from cyclic nucleotides. The hydrolysis of [3H]cIMP by nonactivated enzyme or by preactivated enzyme was linear with time, which indicates that a steady state is reached at the catalytic site within 5 s after addition of the substrate. In contrast, the hydrolysis of [3H]cIMP immediately after activation by 0.1 microM c-b8-GMP was not linear with time, but increased in a quasi-exponential manner with a time constant of 21 s. This suggests that a steady state at the activator site is only reached in 30-45 s after addition of the activator. The on-rate of activation (k1) was 3 X 10(5) M-1s-1 for c-b8-GMP and 1.4 X 10(5) M-1s-1 for cGMP. The off-rate of activation (k-1) was 0.03 s-1 for both c-b8-GMP and cGMP. The significance of these kinetic constants for the chemoattractant-mediated cGMP response in vivo is discussed.


Whole tissue hydrogen sulfide concentrations are orders of magnitude lower than presently accepted values.
Hydrogen sulfide is gaining acceptance as an endogenously produced modulator of tissue function. The present paradigm of H(2)S (diprotonated, gaseous form of hydrogen sulfide) as a tissue messenger consists of H(2)S being released from the desulfhydration of l-cysteine at a rate sufficient to maintain whole tissue hydrogen sulfide concentrations of 30 microM to >100 microM, and these tissue concentrations serve a messenger function. Utilizing physiological concentrations of l-cysteine and aerobic conditions, we found that catabolism of hydrogen sulfide by mouse liver and brain homogenates exceeded the rate of enzymatic release of this compound such that measureable hydrogen sulfide release was less with tissue-containing vs. tissue-free buffers. Analyses of the gas space over rapidly homogenized mouse brain and liver indicated that in situ tissue hydrogen sulfide concentrations were only about 15 nM. Human alveolar air measurements indicated negligible free H(2)S concentrations in blood. We conclude rapid tissue catabolism of hydrogen sulfide maintains whole tissue brain and liver concentrations of free hydrogen sulfide that are three orders of magnitude less than conventionally accepted values and only 1/5,000 of the hydrogen sulfide concentration (100 microM) required to alter cellular function in vitro. For hydrogen sulfide to serve as an endogenously produced messenger, tissue production and catabolism must result in intracellular microenvironments with a sufficiently high hydrogen sulfide concentration to activate a local signaling mechanism, while whole tissue concentrations remain very low.


Effects of monocular deprivation on the structure-function relationship of individual neurons in the cat's lateral geniculate nucleus.
The retino-geniculo-cortical pathways of the cat composed of at least three parallel channels. The neurons in these channels (W-, X-, and Y-cells) have different physiological properties. In earlier studies, we used a direct structure-function for analysis for individual geniculate neurons in normal cats. This was accomplished by electrophysiological characterization of the neuron followed by intracellular iontophoresis of horseradish peroxidase into the same neuron. By this technique, we demonstrated that W-, X-, and Y-cells have distinctive morphological features in the lateral geniculate nucleus of the act. We have extended this analysis in cats reared with monocular eyelid suture to 24 geniculate neurons innervated by the sutured eye in lamina A or A1. Ten of the 24 neurons (42%) had abnormal structure-function relationships. All but 1 of the normal cells were X-cells. Abnormalities included: (1) Y-cells with normal physiology but abnormally small somata; (2) Y-cells with abnormal physiology and morphology, including poor responsiveness and unusually thin, tortuous, and beaded dendrites; (3) visually unresponsive cells with morphology similar to that of the physiologically abnormal Y-cells; and (4) cells with the physiology of normal X-cells but the morphology of normal Y-cells. Furthermore, soma size measurements indicate that the abnormally small somata found in deprived geniculate laminae result from a selective effect on Y-cells.


Prenatal exposure to polybrominated diphenyl ethers and predisposition to frustration at 7 months: Results from the MIREC study.
Prenatal exposure to polybrominated diphenyl ethers (PBDEs) has been associated with cognitive deficits and behavioral problems in children. To date, no study has examined this exposure in association with neurobehavioral development in infants younger than 12 months assessed with observational tasks. This study examined the relation between prenatal PBDE concentrations and predisposition to frustration, assessed by the arm restraint task (ART), in Canadian infants. In a prospective longitudinal study conducted in Canada, exposure to nine PBDE congeners was measured in maternal plasma during the first trimester of pregnancy. The ART was used to measure predisposition to frustration in infancy (N = 333; mean age = 6.9 months), as assessed by negative vocalizations (crying and screaming) and physical reactivity (discomfort movements). Maternal plasma PBDE-47 concentrations collected during pregnancy were associated with negative vocalizations using the ART (adjusted Relative Risk [aRR] = 1.04, 95% CI: 1.00, 1.09). Prenatal PBDE-99 concentrations during pregnancy were also related to a shift to the left in the tail of the distribution of onset of negative vocalizations as measured by a decrease of 38 s (95% CI: -78.1, 1.3) in the 75th quantile of the distribution for infants whose mothers had detectable levels of PBDE-99 compared to infants of mothers with undetectable levels. Similarly, infants whose mothers had detectable levels of PBDE-100 showed an increase of 24.1 s (95% CI: 4.1, 44.1) in the 75th quantile of the distribution of proportion of time in negative vocalizations compared with infants of mothers with undetectable levels. Finally, the association between PBDE-47 and PBDE-153, and physical reactivity was significantly modified by sex (p < 0.1), with opposite patterns in girls and boys. Prenatal exposure to PBDEs was associated with increased incidence of crying and screaming with delayed onset of discomfort movement, which may indicate a predisposition to frustration and lack of habituation in infants younger than 12 months from the general population.


Binaural specialisation in human auditory cortex: an fMRI investigation of interaural correlation sensitivity.
A listener's sensitivity to the interaural correlation (IAC) of sound plays an important role in several phenomena in binaural hearing. Although IAC has been examined humans, little is known about the neural basis of sensitivity to IAC in humans. The present study employed functional magnetic resonance imaging to measure blood oxygen level-dependent (BOLD) activity in auditory brainstem and cortical structures in human listeners during presentation of band-pass noise stimuli between which IAC was varied systematically. The stimuli evoked significant bilateral activation in the inferior colliculus, medial geniculate body, and auditory cortex. There was a significant positive relationship between BOLD activity and IAC which was confined to a distinct subregion of primary auditory cortex located bilaterally at the lateral extent of Heschl's gyrus. Comparison with published anatomical data indicated that this area may also be cytoarchitecturally distinct. Larger differences in activation were found between levels of IAC near unity than between levels near zero. This response pattern is qualitatively compatible with previous measures of psychophysical and neurophysiological sensitivity to IAC. extensively in neurophysiological studies in animals and in psychophysical studies in


[Family experiences of living with chronic schizophrenic patients - application of Parse's human becoming research methodology].
This study was aimed at understanding the nature of the suffering of families with patients in mental health nursing homes and hoped to contribute to the rehabilitation process of those with a chronic mental disorder. Research methodology was based upon Parse's human becoming research methodology. a) Despite the despair the family feels by the violence caused by their now-institutionalized relative, they also realize anew the importance of their role as protectors b) Although they fear social stigmatization they also try to be supportive, out of guilt feelings; c) They regret their severe rearing style and wish to be more sympathetic, d) They find courage and hope through family therapy, which leads to a better understanding of the illness, e) With hopes of rehabilitation, the family members feel happy and go through an emotional release, by sharing the pain with each other. Families of nursing home residents share a focus on the process of human-health-universe. This is a positive, 'human-becoming' process with which, based on past feelings of despair, fear, resignation, and pain, one can render meaning into his or her experiences in the present in the pursuit of love, conquest, hope, liberty and success.


An exon-centric perspective.
During the past ten years, remarkable progress has been made in our understanding of the complexity and regulation of alternative splicing. The generation of large datasets of quantitative alternative splicing profiling information has revealed that transcripts from at least 95% of multi-exon human genes undergo alternative splicing, and that thousands of exons in mammalian transcriptomes are subject to striking regulatory patterns. Together with advanced computational methods, these datasets have enabled the inference of a predictive code for tissue-dependent alternative splicing. This code has further provided new insight into splicing regulatory mechanisms. Collectively, these approaches are revealing the existence of discrete networks of exons that are coordinately regulated in diverse biologically normal and disease contexts. A major challenge ahead is to systematically determine the functions of exons comprising these exon networks as well as the factors and mechanisms responsible for their regulation. This perspective provides an account of progress in these areas and also discusses future avenues of exon-centric exploration.


Development of nanomechanical biosensors for detection of the pesticide DDT.
We report the use of a novel technique for detection of the organochlorine insecticide compound dichlorodiphenyltrichloroethane (DDT) by measuring the nanometer-scale bending of a microcantilever produced by differential surface stress. A synthetic hapten of the pesticide conjugated with bovine serum albumin (BSA) was covalently immobilised on the gold-coated side of the cantilever by using thiol self assembled monolayers. The immobilisation process is characterised by monitoring the cantilever deflection in real-time. Then specific detection is achieved by exposing the cantilever to a solution of a specific monoclonal antibody to the DDT hapten derivative. The specific binding of the antibodies on the cantilever sensitised side is measured with nanomolar sensitivity. Direct detection is proved by performing competitive assays, in which the cantilever is exposed to a mixed solution of the monoclonal antibody and DDT. The future prospects and limitations to be overcome for the application of nanomechanical sensors for pesticide detection are discussed.


Ocular surface changes in glaucomatous patients treated with and without preservatives beta-blockers.
To determine whether there were ocular surface changes in glaucomatous patients treated with preservatives beta-blockers who switched to preservative-free beta-blockers. This was a prospective, longitudinal, open-labeled study. One hundred thirty-two patients with primary open angle glaucoma treated with a preserved beta-blocker were enrolled. All the patients underwent perimetric and gonioscopic examination, complete ophthalmologic examination, intraocular pressure (IOP) measurements, evaluation of ocular surface, Schirmer's test, blood pressure and heart rate at baseline and 1-3 months after changing the medical treatment to a preservative-free timolol 0.1% (Timogel 0.1; Thea). At baseline, after 1 month and at the end of the study (3 months), all patients underwent a questionnaire on the visual quality and symptoms and on the quality of life (QoL). Data were analyzed by t-test when the distribution of the data was normal, by Mann-Whitney when the distribution was not normal. No significant difference was found for IOP before switching from preserved beta-blockers to preservative-free ones. No significant difference was found in blood pressure and heart rate. However, a statistically significant difference was found for abnormal fluorescein staining of the cornea and conjunctiva, eyelid erythema, conjunctival hyperemia, and follicular hyperplasia. A significant difference was found for break-up time (from 9.38±4.7 s at baseline to 10.64±4.7 s after 3 months) and Schirmer's test (from 12.9±5.96 mm at baseline to 14.2±5.87 mm after 3 months). The questionnaire showed that the patient improved the dryness and foreign body sensation. In glaucomatous patients, preservative-free 0.1 timolol treatment improved their QoL. Similar dry eye signs or symptoms improved after 3 months of treatment reducing dryness, hyperemia, follicular hyperplasia, and foreign body sensation.


Cytotoxicity and anti-inflammatory effects of zinc ions and eugenol during setting of ZOE in immortalized human oral keratinocytes grown as three-dimensional spheroids.
The objective of this study is to assess the cytotoxic and anti-inflammatory effects of ZOE cement during setting in two-dimensional (2D) or three-dimensional (3D) cultures of immortalized human oral keratinocytes (IHOKs) with determining the extract components responsible for these effects. Extracts of mixed ZOE at different stages of setting were analyzed by a digital pH meter, ICP-MS, and GC-MS. Serial concentrations of extract and their mixture of ZnCl2, ZnSO4·H2O, and eugenol liquid were added to the 2D and 3D IHOK cultures to determine the half maximal effective concentration in investigating the cause of cytotoxicity by means of WST assay and to investigate mRNA expression levels of inflammatory cytokines by RT-PCR. Zn(2+) and eugenol (4-19 ppm) were detected in the extracts. In the early setting stage, significant cytotoxicity was observed in the 2D and 3D IHOK cultures (P<0.05). The EC50 of Zn(2+) from ZnCl2 was 5-44 ppm in both cultures, whereas the EC50 of eugenol was not detectable under 100 ppm. Along with the lower levels of inflammatory cytokine gene expressions in the extract, treatment of the 2D IHOKs with Zn(2+) alone and treatment of the 3D IHOKs with Zn(2+) plus eugenol resulted in significantly lower expression levels of IL-1β, IL-6, and IL-8 (P<0.05). The cytotoxic effect of ZOE on IHOKs was greater during the setting stage owing to the presence of Zn(2+). The anti-inflammatory response to ZOE was induced by a combination of Zn(2+) and eugenol. Cytotoxic and anti-inflammatory effects differed between the 2D and 3D IHOK cultures.


SCPEM-Q-switching of a fiber-rod-laser.
We demonstrate high-frequency Q-switching of a fiber rod laser with a Single-Crystal Photo-Elastic Modulator (SCPEM) made of a LiTaO₃₋ crystal. This type of photo-elastic modulator can be driven simultaneously with two different eigenmodes to achieve a shorter rise time, which is essential for high-power operation. When operated in the laser cavity, a pulse repetition frequency of 183.6 kHz with an average power of 47 W, a pulse duration of 26 ns, and a peak power of 10.5 kW was achieved.


The impact of the Benign Brain Tumor Cancer Registries Amendment Act (Public Law 107-260) on non-malignant brain and central nervous system tumor incidence trends.
The study objective was to investigate patterns of reported non-malignant brain and CNS tumor incidence over a time period encompassing 1997-2008 during which time the Benign Brain Tumor Cancer Registries Amendment Act (PL 107-260) was passed and implemented. Analyses of 75,350 incident non-malignant brain and CNS tumors from eleven population-based central registries revealed that there were statistically significant increases in the age-adjusted incidence rate for non-malignant tumors for those diagnosed prior to 2002 and over the time period from 2002 until 2005. However, no significant change in the age-adjusted incidence rate for non-malignant tumors was observed over the time period 2005 to 2008 indicating that the incidence from this time period may quantify the "true" incidence of non-malignant brain and CNS tumors in the United States.


Phenomenological Reliving and Visual Imagery During Autobiographical Recall in Alzheimer's Disease.
Multiple studies have shown compromise of autobiographical memory and phenomenological reliving in Alzheimer's disease (AD). We investigated various phenomenological features of autobiographical memory to determine their relative vulnerability in AD. To this aim, participants with early AD and cognitively normal older adult controls were asked to retrieve an autobiographical event and rate on a five-point scale metacognitive judgments (i.e., reliving, back in time, remembering, and realness), component processes (i.e., visual imagery, auditory imagery, language, and emotion), narrative properties (i.e., rehearsal and importance), and spatiotemporal specificity (i.e., spatial details and temporal details). AD participants showed lower general autobiographical recall than controls, and poorer reliving, travel in time, remembering, realness, visual imagery, auditory imagery, language, rehearsal, and spatial detail-a decrease that was especially pronounced for visual imagery. Yet, AD participants showed high rating for emotion and importance. Early AD seems to compromise many phenomenological features, especially visual imagery, but also seems to preserve some other features.


Who uses the services of pediatric dentists?
Parents and guardians reported almost 120 million dental visits in 1983 for children between two and seventeen years of age. Pediatric dentists provided nearly 19 percent of visits for two-to four-year-olds; 9 percent for children between five and eleven years; and 1.4 percent for children between twelve and seventeen years of age.


Intrapopulational variation in the standard metabolic rate of insects: repeatability, thermal dependence and sensitivity (Q10) of oxygen consumption in a cricket.
Studies focusing on physiological variation among individuals, and its possible evolutionary consequences, are scarce. A trait can only be a target of natural selection if it is consistent over time, that is, a trait must be repeatable. In ectotherms it has been suggested that standard metabolic rate (MR) is related to Darwinian fitness, since it reflects energy usage and expenditure. The metabolic rate of the cricket Hophlosphyrum griseus was determined at three ambient temperatures. Repeatability of MR was estimated by product-moment correlation on residuals of body mass, as well as the thermal sensitivity of MR on an individual basis (individual Q(10)). The MR of H. griseus was significantly repeatable (r=0.53) and highly dependent on ambient temperature, and its sensitivity (Q(10)) was dependent on the temperature range. Our estimation of MR repeatability was high in comparison to published studies in vertebrates. Ours is the second report of repeatability (i.e. consistency over time of an individual's performance ranking within a population) of any aspect of energy metabolism in an insect, and also the first study to report significant repeatability of MR. Individual Q(10) values revealed important interindividual variation, which reflects the existence of intrapopulational variability in the thermal sensitivity of MR. In addition, individual Q(10) values were negatively correlated between temperature ranges. This means that crickets having low Q(10) at low temperatures, presented high Q(10) at high temperatures, and vice versa. Our results suggest that MR could be of selective value in insects, showing consistency over time and intrapopulational variability in its thermal dependence. Nevertheless, its heritability remains to be determined.


[Organization and management of Norwegian intensive care units].
A survey of organisational and managerial aspects in Norwegian intensive care units (ICU) was made six months after Standards for Intensive Care, a document setting out guidelines for the organisation and management of intensive care units, had been issued by the Norwegian Medical Association to Norwegian hospitals. 298 questionnaires were sent to hospital managers and heads of clinical departments in 58 Norwegian hospitals. The overall response rate was 77%. 60% of the respondents had heard about Standards, 44% had read them, 15% used them. The majority of ICUs were run by the Department of Anaesthesia. 75% answered that the admitting department had the overall responsibility for the individual patient; 23% of respondents claimed that the ICU doctor was responsible. More than half of these worked in secondary and tertiary care hospitals. Standards of Intensive Care is poorly known and read by less than half of the respondents. Only a few have started to implement them. Some uncertainty about patient responsibility may exist particularly in secondary and tertiary care hospitals. There seems to be a need for better role clarification and definitions of responsibility for all participants in intensive care, with more focus on organisational and managerial aspects.


Surface acoustic wave microfluidics.
The recent introduction of surface acoustic wave (SAW) technology onto lab-on-a-chip platforms has opened a new frontier in microfluidics. The advantages provided by such SAW microfluidics are numerous: simple fabrication, high biocompatibility, fast fluid actuation, versatility, compact and inexpensive devices and accessories, contact-free particle manipulation, and compatibility with other microfluidic components. We believe that these advantages enable SAW microfluidics to play a significant role in a variety of applications in biology, chemistry, engineering and medicine. In this review article, we discuss the theory underpinning SAWs and their interactions with particles and the contacting fluids in which they are suspended. We then review the SAW-enabled microfluidic devices demonstrated to date, starting with devices that accomplish fluid mixing and transport through the use of travelling SAW; we follow that by reviewing the more recent innovations achieved with standing SAW that enable such actions as particle/cell focusing, sorting and patterning. Finally, we look forward and appraise where the discipline of SAW microfluidics could go next.


Coronavirus Disease 2019 (COVID-19) Infection Among People With Human Immunodeficiency Virus in New York City: A Population-Level Analysis of Linked Surveillance Data.
New York City (NYC) was hard-hit by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and is also home to a large population of people with human immunodeficiency virus (PWH). We matched laboratory-confirmed coronavirus disease 2019 (COVID-19) case and death data reported to the NYC Health Department as of 2 June 2020 against the NYC HIV surveillance registry. We describe and compare the characteristics and COVID-19-related outcomes of PWH diagnosed with COVID-19 with all NYC PWH and with all New Yorkers diagnosed with COVID-19. Through 2 June, 204 583 NYC COVID-19 cases were reported. The registry match identified 2410 PWH with diagnosed COVID-19 eligible for analysis (1.06% of all COVID-19 cases). Compared with all NYC PWH and all New Yorkers diagnosed with COVID-19, a higher proportion of PWH with COVID-19 were older, male, Black, or Latino, and living in high-poverty neighborhoods. At least 1 underlying condition was reported for 58.9% of PWH with COVID-19. Compared with all NYC COVID-19 cases, a higher proportion of PWH with COVID-19 experienced hospitalization, intensive care unit admission, and/or death; most PWH who experienced poor COVID-19-related outcomes had CD4 <500 cells/µL. Given NYC HIV prevalence is 1.5%, PWH were not overrepresented among COVID-19 cases. However, compared with NYC COVID-19 cases overall, a greater proportion of PWH had adverse COVID-19-related outcomes, perhaps because of a higher prevalence of factors associated with poor COVID-19 outcomes. Given the pandemic's exacerbating effects on health inequities, HIV public health and clinical communities must strengthen services and support for people living with and affected by HIV.


Capsule endoscopy for the detection of oesophageal mucosal disorders: a comparison of two different ingestion protocols.
To assess the accuracy of a new ingestion protocol for capsule endoscopy (CE) in evaluating patients with gastro-oesophageal reflux disease (GORD). Oesophago-gastroduodenoscopy (OGD) was performed 1 week prior to CE. The first 28 subjects swallowed the capsule following the original ingestion protocol (OIP) and the subsequent 30 subjects following a simplified ingestion protocol (SIP). CE videos were reviewed by two independent investigators who were blinded to the OGD findings. Of 48 patients included, 24 were diagnosed with reflux oesophagitis (67% male, mean age 49.5+/-13 years) and 24 with Barrett oesophagus (BO) (88% male, 55.6+/-10 years) by OGD. In addition, 10 asymptomatic healthy controls (50% male, 45.8+/-7.1 years) were included. Oesophageal transit time was faster in patients using the SIP compared to the OIP (126+/-26 s versus 214+/-33; p=0.04). Complete evaluation of the Z-line was possible in 19/28 (68%) of the OIPs compared to 28/30 (93%) of the SIPs (p=0.04). Sensitivity for detecting any oesophageal abnormality was higher in the SIP group than in the OIP group (97% versus 89%; p=0.11). Overall, CE detected oesophagitis in 22/24 patients (sensitivity, 92%; specificity, 88%) and BO in 23/24 patients (sensitivity, 96%; specificity, 91%). Furthermore, 41/44 (93%) preferred CE over OGD and experienced less discomfort and pain during CE. CE is an accurate method for detecting mucosal oesophageal abnormalities. The new ingestion protocol improves the visualization of the Z-line, which is likely to increase the diagnostic yield of CE.


Complications of splintage in congenital dislocation of the hip.
The use of abduction splintage in the treatment of congenital dislocation of the hip has an important morbidity. Six children who developed complications are presented in this paper. Sustained splintage of an unreduced hip, overcorrection of the femoral head displacement, avascular necrosis of the femoral head, full thickness pressure sores, and excessive tibial torsion may occur as a consequence of treatment. Expert supervision of abduction splintage, correct case selection, and regular review are necessary to reduce the incidence of such complications.


[Pulmonary doppler. Early results in normal pregnancies].
The study of fetal lung circulation by means of pulmonary Doppler investigation. Pulmonary Doppler ultrasound obtained with color pulsed-Doppler with a 3.5-5 Mhz probe. Measure of resistance index and pulsatility index. Forty seven pregnant women with singleton, between 18 and 39.5 weeks gestation, were recruited to have a pulmonary Doppler ultrasound. 7 fetuses had intra uterine fetal growth retardation (IUGR). Overall, 50 Doppler velocity waveforms were measured. Resistance and pulsatility index were measured in all patients and at each examination. Resistance index (0.86 +/- 0.03) and pulsatility index (2.46 +/- 0.34) were found to be stable during pregnancy. Pulmonary pulsatility index in IUGR fetuses (2.71 +/- 0.33) were found to be higher than those in normotrophic infants (p = 0.006), whereas no difference was found in resistance index between the same subgroups. Moreover, no difference was found in pulsatility index measurements between preterm small-for-gestational age fetuses and normotrophic fetuses measured between 36 and 39.5 weeks gestation (2.68 +/- 0.31 vs 2.49 +/- 0.28). Pulmonary resistance index is not statistically different between nomotrophic and IUGR fetuses. In contrast pulmonary pulsatility index is significantly higher in IUGR fetuses when compared with normotrophic fetuses. Pulmonary Doppler ultrasound should be evaluated in a larger trial and correlation between Doppler measurements and fetal lung maturation should be studied.


Surgical Infection Society Guidance for Operative and Peri-Operative Care of Adult Patients Infected by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).
Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-associated viral infection (coronavirus disease 2019, COVID-19) is a virulent, contagious viral pandemic that is affecting populations worldwide. As with any airborne viral respiratory infection, surgical and non-surgical patients may be affected. Methods: Review and synthesis of pertinent English-language literature pertaining to COVID-19 infection among adult patients. Results: COVID-19 disease that requires hospitalization results in critical illness approximately 25% of the time and requires mechanical ventilation with positive airway pressure. Acute kidney injury, a marked hypercoagulable state, and sometimes myocarditis can be features of COVID-19 in addition to the characteristic severe acute lung injury. Even if not among the most seriously afflicted, older patients with medical comorbidities are both predisposed to infection and risk increased morbidity and mortality, however, all persons presenting for surgical intervention should be suspected of infection (and thus transmissibility) even if asymptomatic. Although most elective surgery has been curtailed by administrative or governmental fiat, patients will still need urgent or emergency operative intervention for time-sensitive disease processes such as malignant neoplasia or for true emergencies such as perforated viscus or traumatic injury. It is possible to provide safe surgical care for SARS-CoV-2-positive patients and minimize nosocomial transmission to healthcare workers. Conclusions: This guidance will facilitate appropriate protection of patients and staff, and maintenance of infection control measures to assist surgical personnel and facilities to prepare for COVID-19-infected adult patients requiring urgent or emergent operative intervention and to provide optimal patient care.


Once- versus twice-daily venlafaxine therapy in major depression: a randomized, double-blind study.
Psychotropic drug dosing regimens are often based on the pharmacokinetic elimination half-life of the compound. This implies that the pharmacokinetic half-life of the drug may be the critical or sole determinant of pharmacodynamic half-life. In the present study, we examined the safety and efficacy of once- versus twice-daily dosing regimens of the immediate-release formulation of venlafaxine, a serotonin and norepinephrine reuptake site blocker with a short elimination half-life. Forty-eight patients with a diagnosis of DSM-IV major depressive episode were randomly assigned to once-daily (N = 25) versus twice-daily (N = 23) venlafaxine. Venlafaxine was started at 37.5 mg daily with specified increments up to 225 mg daily. Efficacy was rated using the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions scale (CGI). Twenty-one patients in each group completed 6 weeks of treatment. We observed a significant reduction in mean weekly HAM-D and MADRS scores at weeks 1 through 6 for both dosing groups (p < .001). There were no statistically significant differences in mean HAM-D or MADRS scores between dosing groups at any time point. There was, however, a nonsignificant trend for a more rapid reduction in the mean HAM-D score at week 2 (p < .06) and in the mean MADRS score at week 1 (p < .07) and week 2 (p < .09) in the b.i.d. dosing group. Similarly, there was a significant decrease in the CGI score at week 2 (p < .02) in the b.i.d. dosing group. The rate of adverse events was similar between treatment groups; the most common adverse events were transient nausea and headaches. These results indicate that the immediate-release formulation of venlafaxine may be safe and effective in some patients when used in a once-daily dose regimen. Moreover, the present results suggest that the short elimination half-life of immediate-release venlafaxine should not be the sole determinant for multiple daily dosing and that antidepressant activity may be more profoundly influenced by a drug's pharmacodynamic half-life than by its pharmacokinetic half-life.


Mild nasal clefting may be predictive for ALX4 heterozygotes.
Heterozygous loss-of-function mutations in ALX4 are responsible for enlarged parietal foramina, whereas patients with biallelic ALX4 mutations display a phenotypic spectrum of clinical findings, from mild to severe alopecia, cranium bifidum, hypertelorism, microphthalmia, with alar clefting being the pivotal sign in all affecteds. We report on four affected individuals in a three-generation family, displaying a phenotypic spectrum ranging from mild nasal clefting and broad columella to subtle changes in nasal configuration in addition to parietal foramina, caused by a novel ALX4 mutation (c.646C>G, p.Arg216Gly). This is the second report of a family showing vertical transmission of a dominant ALX4 mutation with facial involvement in addition to parietal foramina, mimicking mild recessive ALX4 phenotype. We discuss possible pathological mechanisms that may have lead to phenotypic variation in the family and challenges in genetic counseling.


The epidemiology of community paediatric outpatient referrals 2006.
Wirral University Teaching Hospital is a large district general hospital situated on the Wirral Peninsula, UK. Because of the district's geographical and demographic characteristics, Wirral is an ideal location for population-based studies. Information on community paediatric referrals, case mix and outcomes is scarce. We took advantage of our situation to conduct an epidemiological study of referrals to community paediatrics in Wirral. A companion paper examines referrals to general paediatricians during the same period. A prospective observational study of community paediatric outpatient referrals between 1 February and 31 May 2006 for all children under the age of 15 offered a new patient appointment during the study period. The study was conducted using the same methodology as a previous population-based study of community paediatric outpatients in Northampton, UK in 1998. We compared our results with this previous study. The referral rate was 10.1 per 1000 children under 15 per annum. School nurses and health visitors made nearly half the referrals, with general practitioners referring most of the remainder. Compared with the Northampton study, more children were seen by consultants. Case mix showed a shift towards behavioural and neurodevelopmental disorders, with less general paediatrics. Attention deficit hyperactivity disorder was the commonest disorder seen (28.2%), a significant increase from the previous study (3.4%) (P < 0.01). Autism spectrum disorder showed little change (8.1% vs. 9.6%; NS). The Wirral study showed significantly more follow-up compared with the Northampton. This population-based study gives a unique insight into the epidemiology of referrals to community paediatricians in the UK in 2006 and how these differ from those recorded in a different UK district in 1998.


Inferring genetic interactions via a nonlinear model and an optimization algorithm.
Biochemical pathways are gradually becoming recognized as central to complex human diseases and recently genetic/transcriptional interactions have been shown to be able to predict partial pathways. With the abundant information made available by microarray gene expression data (MGED), nonlinear modeling of these interactions is now feasible. Two of the latest advances in nonlinear modeling used sigmoid models to depict transcriptional interaction of a transcription factor (TF) for a target gene, but do not model cooperative or competitive interactions of several TFs for a target. An S-shape model and an optimization algorithm (GASA) were developed to infer genetic interactions/transcriptional regulation of several genes simultaneously using MGED. GASA consists of a genetic algorithm (GA) and a simulated annealing (SA) algorithm, which is enhanced by a steepest gradient descent algorithm to avoid being trapped in local minimum. Using simulated data with various degrees of noise, we studied how GASA with two model selection criteria and two search spaces performed. Furthermore, GASA was shown to outperform network component analysis, the time series network inference algorithm (TSNI), GA with regular GA (GAGA) and GA with regular SA. Two applications are demonstrated. First, GASA is applied to infer a subnetwork of human T-cell apoptosis. Several of the predicted interactions are supported by the literature. Second, GASA was applied to infer the transcriptional factors of 34 cell cycle regulated targets in S. cerevisiae, and GASA performed better than one of the latest advances in nonlinear modeling, GAGA and TSNI. Moreover, GASA is able to predict multiple transcription factors for certain targets, and these results coincide with experiments confirmed data in YEASTRACT. GASA is shown to infer both genetic interactions and transcriptional regulatory interactions well. In particular, GASA seems able to characterize the nonlinear mechanism of transcriptional regulatory interactions (TIs) in yeast, and may be applied to infer TIs in other organisms. The predicted genetic interactions of a subnetwork of human T-cell apoptosis coincide with existing partial pathways, suggesting the potential of GASA on inferring biochemical pathways.


Serum metabolic profiles of septic shock patients based upon co-morbidities and other underlying conditions.
Diagnosis and management of patients with septic shock is still a significant challenge for clinicians with its high mortality amongst hospitalized patients. Septic shock is a heterogeneous condition and is usually accompanied by various underlying disease conditions. Dissecting the specific metabolic changes induced by these underlying disease conditions through metabolomics has shown the potential to improve our understanding of the disease's relevant pathophysiological mechanisms, leading to improved treatment. This study has shown the metabolic alterations caused due to co-morbid conditions like diabetes, hypertension, CAD, and CKD in septic shock. It has also shown the distinct metabolic profiles of septic shock patients with underlying respiratory illnesses and encephalopathy. Metabolic profiling of sera obtained from 50 septic shock patients and 20 healthy controls was performed using high-resolution 1D 1H CPMG and diffusion-edited NMR spectra. Univariate and multivariate statistical analyses were performed to identify the potential molecular biomarkers. Noted dysregulations in amino acids, carbohydrates, and lipid metabolism were observed in septic shock patients. Further stratification within the septic shock patients based on co-morbid conditions and primary diagnosis has shown their role in causing metabolic alterations. Evaluation of these compounds during treatment will help design a personalized treatment protocol for the patients, improving therapeutics.


Drug-related decrease in neuropsychological functions of abstinent drug users.
This article reviews neuropsychological performance in frequent users of cocaine, (meth)amphetamines, ecstasy, opiates, alcohol, and cannabis. We searched the scientific literature published in the last five years, focusing on studies that required at least 2 weeks of abstinence from drug use, and included a control group. All substances of abuse, except cannabis, were associated with sustained deficits in executive functioning, especially inhibition. In addition, verbal memory decrements were consistently found in cocaine, (meth)amphetamines and ecstasy users, but not in heroin or cannabis users. More specific executive functioning deficits were reported depending on the substance of abuse. Cocaine was associated with diminished cognitive flexibility, whereas (meth)amphetamines were associated with worse cognitive planning functions compared to controls. Opiate studies showed lower scores on verbal fluency in opiate dependent subjects compared to controls. Working memory and visuospatial abilities were compromised in alcohol abusers. In ecstasy users, inconsistent findings have been reported across neuropsychological domains, with the exception of inhibition and verbal memory. There was little evidence for sustained cognitive impairments in adult abstinent cannabis users. Recognition of neuropsychological problems related to different substances can help to select subjects that will benefit most from treatment. Furthermore, a better understanding of the neuropsychological impairments in drug abusing individuals could help to explain the remitting course of substance abuse disorders and to improve psychological interventions.


Review article: drug-induced pancreatitis.
Drugs are a relatively uncommon cause of pancreatitis in adult patients, but should be considered when other reasonable causes of pancreatitis are not present. A wide variety of drugs have been reported to cause pancreatitis. Drug-induced pancreatitis is almost always acute and may be mild to fatal in severity. Definite proof that a drug causes pancreatitis requires that pancreatitis develops during treatment with the drug, that other likely causes of pancreatitis are not present, that pancreatitis resolves upon discontinuing the drug, and that pancreatitis usually recurs upon readministration of the drug. For ethical reasons, rechallenge with the suspect drug can be done only if the drug is necessary to treat a serious condition; thus this highly convincing piece of evidence relating the drug to pancreatitis may not be available. Information about drug-related pancreatitis is often not readily available, particularly for newer drugs. Clinicians should consider obtaining information directly from regulatory agencies and manufacturers as well as the literature.


Altered macrophage phenotype transition impairs skeletal muscle regeneration.
Monocyte/macrophage polarization in skeletal muscle regeneration is ill defined. We used CD11b-diphtheria toxin receptor transgenic mice to transiently deplete monocytes/macrophages at multiple stages before and after muscle injury induced by cardiotoxin. Fat accumulation within regenerated muscle was maximal when ablation occurred at the same time as cardiotoxin-induced injury. Early ablation (day 1 after cardiotoxin) resulted in the smallest regenerated myofiber size together with increased residual necrotic myofibers and fat accumulation. However, muscle regeneration after late (day 4) ablation was similar to controls. Levels of inflammatory cells in injured muscle following early ablation and associated with impaired muscle regeneration were determined by flow cytometry. Delayed, but exaggerated, monocyte [CD11b(+)(CD90/B220/CD49b/NK1.1/Ly6G)(-)(F4/80/I-Ab/CD11c)(-)Ly6C(+/-)] accumulation occurred; interestingly, Ly6C(+) and Ly6C(-) monocytes were present concurrently in ablated animals and control mice. In addition to monocytes, proinflammatory, Ly6C(+) macrophage accumulation following early ablation was delayed compared to controls. In both groups, CD11b(+)F4/80(+) cells exhibited minimal expression of the M2 markers CD206 and CD301. Nevertheless, early ablation delayed and decreased the transient accumulation of CD11b(+)F4/80(+)Ly6C(-)CD301(-) macrophages; in control animals, the later tissue accumulation of these cells appeared to correspond to that of anti-inflammatory macrophages, determined by cytokine production and arginase activity. In summary, impairments in muscle regeneration were associated with exaggerated monocyte recruitment and reduced Ly6C(-) macrophages; the switch of macrophage/monocyte subsets is critical to muscle regeneration.


Physiological effects of five different marine natural organic matters (NOMs) and three different metals (Cu, Pb, Zn) on early life stages of the blue mussel (Mytilus galloprovincialis).
Metals are present in aquatic environments as a result of natural and anthropogenic inputs, and may induce toxicity to organisms. One of the main factors that influence this toxicity in fresh water is natural organic matter (NOM) but all NOMs are not the same in this regard. In sea water, possible protection by marine NOMs is not well understood. Thus, our study isolated marine NOMs by solid-phase extraction from five different sites and characterized them by excitation-emission fluorescence analysis-one inshore (terrigenous origin), two offshore (autochthonous origin), and two intermediate in composition (indicative of a mixed origin). The physiological effects of these five NOMS alone (at 8 mg/L), of three metals alone (copper, lead and zinc at 6 µg Cu/L, 20 µg Pb/L, and 25 µg Zn/L respectively), and of each metal in combination with each NOM, were evaluated in 48-h exposures of mussel larvae. Endpoints were whole body Ca2++Mg2+-ATPase activity, carbonic anhydrase activity and lipid peroxidation. By themselves, NOMs increased lipid peroxidation, Ca2++Mg2+-ATPase, and/or carbonic anhydrase activities (significant in seven of 15 NOM-endpoint combinations), whereas metals by themselves did not affect the first two endpoints, but Cu and Pb increased carbonic anhydrase activities. In combination, the effects of NOMs predominated, with the metal exerting no additional effect in 33 out of 45 combinations. While NOM effects varied amongst different isolates, there was no clear pattern with respect to optical or chemical properties. When NOMs were treated as a single source by data averaging, NOM had no effect on Ca2++Mg2+-ATPase activity but markedly stimulated carbonic anhydrase activity and lipid peroxidation, and there were no additional effects of any metal. Our results indicate that marine NOMs may have direct effects on this model marine organism, as well as protective effects against metal toxicity, and the quality of marine NOMs may be an important factor in these actions.


Allophonic mode of speech perception in dyslexia.
Perceptual discrimination between speech sounds belonging to different phoneme categories is better than that between sounds falling within the same category. This property, known as "categorical perception," is weaker in children affected by dyslexia. Categorical perception develops from the predispositions of newborns for discriminating all potential phoneme categories in the world's languages. Predispositions that are not relevant for phoneme perception in the ambient language are usually deactivated during early childhood. However, the current study shows that dyslexic children maintain a higher sensitivity to phonemic distinctions irrelevant in their linguistic environment. This suggests that dyslexic children use an allophonic mode of speech perception that, although without straightforward consequences for oral communication, has obvious implications for the acquisition of alphabetic writing. Allophonic perception specifically affects the mapping between graphemes and phonemes, contrary to other manifestations of dyslexia, and may be a core deficit.


Collaborative Research Project: Developing and Testing a Robot-Assisted Intervention for Children With Autism.
The present work is a collaborative research aimed at testing the effectiveness of the robot-assisted intervention administered in real clinical settings by real educators. Social robots dedicated to assisting persons with autism spectrum disorder (ASD) are rarely used in clinics. In a collaborative effort to bridge the gap between innovation in research and clinical practice, a team of engineers, clinicians and researchers working in the field of psychology developed and tested a robot-assisted educational intervention for children with low-functioning ASD (N = 20) A total of 14 lessons targeting requesting and turn-taking were elaborated, based on the Pivotal Training Method and principles of Applied Analysis of Behavior. Results showed that sensory rewards provided by the robot elicited more positive reactions than verbal praises from humans. The robot was of greatest benefit to children with a low level of disability. The educators were quite enthusiastic about children's progress in learning basic psychosocial skills from interactions with the robot. The robot nonetheless failed to act as a social mediator, as more prosocial behaviors were observed in the control condition, where instead of interacting with the robot children played with a ball. We discuss how to program robots to the distinct needs of individuals with ASD, how to harness robots' likability in order to enhance social skill learning, and how to arrive at a consensus about the standards of excellence that need to be met in interdisciplinary co-creation research. Our intuition is that robotic assistance, obviously judged as to be positive by educators, may contribute to the dissemination of innovative evidence-based practice for individuals with ASD.


Unexpected contribution of lymphatic vessels to promotion of distant metastatic tumor spread.
Tumor lymphangiogenesis is accompanied by a higher incidence of sentinel lymph node metastasis and shorter overall survival in several types of cancer. We asked whether tumor lymphangiogenesis might also occur in distant organs with established metastases and whether it might promote further metastatic spread of those metastases to other organs. Using mouse metastasis models, we found that lymphangiogenesis occurred in distant lung metastases and that some metastatic tumor cells were located in lymphatic vessels and draining lymph nodes. In metastasis-bearing lungs of melanoma patients, a higher lymphatic density within and around metastases and lymphatic invasion correlated with poor outcome. Using a transgenic mouse model with inducible expression of vascular endothelial growth factor C (VEGF-C) in the lung, we found greater growth of lung metastases, with more abundant dissemination to other organs. Our findings reveal unexpected contributions of lymphatics in distant organs to the promotion of growth of metastases and their further spread to other organs, with potential clinical implications for adjuvant therapies in patients with metastatic cancer.


[Effect of 1,25-dihydroxyvitamin D3 on 15-lipoxygenase activity].
The influence of 1.25-dihydroxyvitamin D3 on soybean 15-lipoxygenase activity was studied in vitro. 1.25-Dihydroxyvitamin D3 inhibited enzymatic activity in relation to its dose, pH and substrate (linoleic acid) concentration; the findings are indicative of a mixed type of inhibition.


[Is hip sonography meaningful as a screening method?].
The results of screening 162 non-selected neonates by sonography of the hips indicate that this is not a desirable screening method. Sonography is, however, indicted in neonatal groups which are considered to be at risk.


Methodology for developing quality indicators for the care of older people in the Emergency Department.
Compared with younger people, older people have a higher risk of adverse health outcomes when presenting to emergency departments. As the population ages, older people will make up an increasing proportion of the emergency department population. Therefore it is timely that consideration be given to the quality of care received by older persons in emergency departments, and to consideration of those older people with special needs. Particular attention will be focused on important groups of older people, such as patients with cognitive impairment, residents of long term care and patients with palliative care needs. This project will develop a suite of quality indicators focused on the care of older persons in the emergency department. Following input from an expert panel, an initial set of structural, process, and outcome indicators will be developed based on thorough systematic search in the scientific literature. All initial indicators will be tested in eight emergency departments for their validity and feasibility. Results of the data from the field studies will be presented to the expert panel at a second meeting. A suite of Quality Indicators for the older emergency department population will be finalised following a formal voting process. The predicted burgeoning in the number of older persons presenting to emergency departments combined with the recognised quality deficiencies in emergency department care delivery to this population, highlight the need for a quality framework for the care of older persons in emergency departments. Additionally, high quality of care is associated with improved survival & health outcomes of elderly patients. The development of well-selected, validated and economical quality indicators will allow appropriate targeting of resources (financial, education or quality management) to improve quality in areas with maximum potential for improvement.


Interaction of green tea polyphenols with dairy matrices in a simulated gastrointestinal environment.
The consumption of polyphenols in green tea has been associated with beneficial health effects. Although polyphenols are unstable in the intestinal environment, they may be protected by interactions with dairy proteins during digestion. The objectives of this study were to evaluate the effect of a green tea extract on the digestibility of different dairy matrices and to monitor the antioxidant activity of these matrices with or without the green tea extract during digestion in a simulated gastrointestinal environment. Milk, yogurt and cheese with similar fat-to-protein ratios were subjected to simulated digestion. Matrix degradation, protein and fat hydrolysis, polyphenol concentration and radical scavenging activity were analyzed during gastric and intestinal digestion phases. Cheese was the matrix most resistant to protein and fat digestion. The addition of the green tea extract significantly decreased proteolysis in the gastric phase but had no effect in the intestinal phase. The kinetics of fatty acid release was reduced by the presence of the green tea extract. Transition from the gastric phase to the intestinal phase induced a 50% decrease in the antioxidant activity of the control (tea extract dispersed in water) due to the degradation of polyphenols. The presence of dairy matrices significantly improved polyphenol stability in the intestinal phase and increased the antioxidant activity by 29% (cheese) to 42% (milk) compared to the control. These results suggest that simultaneous consumption of green tea and dairy products helps to maintain the integrity and antioxidant activity of polyphenols during digestion.


The surgery of epilepsy.
The idea of surgical treatment for epilepsy is not new. However, widespread use and general acceptance of this treatment has only been achieved during the past three decades. A crucial step in this direction was the development of video electroencephalographic monitoring. Improvements in imaging resulted in an increased ability for preoperative identification of intracerebral and potentially epileptogenic lesions. High resolution magnetic resonance imaging plays a major role in structural and functional imaging; other functional imaging techniques (e.g., positron emission tomography and single-photon emission computed tomography) provide complementary data and, together with corresponding electroencephalographic findings, result in a hypothesis of the epileptogenic lesion, epileptogenic zone, and the functional deficit zone. The development of microneurosurgical techniques was a prerequisite for the general acceptance of elective intracranial surgery. New less invasive and safer resection techniques have been developed, and new palliative and augmentative techniques have been introduced. Today, epilepsy surgery is more effective and conveys a better seizure control rate. It has become safer and less invasive, with lower morbidity and mortality rates. This article summarizes the various developments of the past three decades and describes the present tools for presurgical evaluation and surgical strategy, as well as ideas and future perspectives for epilepsy surgery.


Evolution of heliobacteria: Implications for photosynthetic reaction center complexes.
The evolutionary position of the heliobacteria, a group of green photosynthetic bacteria with a photosynthetic apparatus functionally resembling Photosystem I of plants and cyanobacteria, has been investigated with respect to the evolutionary relationship to Gram-positive bacteria and cyanobacteria. On the basis of 16S rRNA sequence analysis, the heliobacteria appear to be most closely related to Gram-positive bacteria, but also an evolutionary link to cyanobacteria is evident. Interestingly, a 46-residue domain including the putative sixth membrane-spanning region of the heliobacterial reaction center protein shows rather strong similarity (33% identity and 72% similarity) to a region including the sixth membrane-spanning region of the CP47 protein, a chlorophyll-binding core antenna polypeptide of Photosystem II. The N-terminal half of the heliobacterial reaction center polypeptide shows a moderate sequence similarity (22% identity over 232 residues) with the CP47 protein, which is significantly more than the similarity with the Photosystem I core polypeptides in this region. An evolutionary model for photosynthetic reaction center complexes is discussed, in which an ancestral homodimeric reaction center protein (possibly resembling the heliobacterial reaction center protein) with 11 membrane-spanning regions per polypeptide has diverged to give rise to core of Photosystem I, Photosystem II, and of the photosynthetic apparatus in green, purple, and heliobacteria.


Characterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancer.
Cyclin D1 (Ccnd1) is a proto-oncogen amplified in many different cancers and nuclear accumulation of Ccnd1 is a characteristic of tumor cells. Ccnd1 activates the transcription of a large set of genes involved in cell cycle progress and proliferation. However, Ccnd1 also targets cytoplasmic proteins involved in the regulation of cell migration and invasion. In this work, we have analyzed by immunohistochemistry the localization of Ccnd1 in endometrial, breast, prostate and colon carcinomas with different types of invasion. The number of cells displaying membranous or cytoplasmic Ccnd1 was significantly higher in peripheral cells than in inner cells in both collective and pushing invasion patterns of endometrial carcinoma, and in collective invasion pattern of colon carcinoma. Also, the cytoplasmic localization of Ccnd1 was higher when tumors infiltrated as single cells, budding or small clusters of cells. To evaluate cytoplasmic function of cyclin D1, we have built a variant (Ccnd1-CAAX) that remains attached to the cell membrane therefore sequestering this cyclin in the cytoplasm. Tumor cells harboring Ccnd1-CAAX showed high levels of invasiveness and metastatic potential compared to those containing the wild type allele of Ccnd1. However, Ccnd1-CAAX expression did not alter proliferative rates of tumor cells. We hypothesize that the role of Ccnd1 in the cytoplasm is mainly associated with the invasive capability of tumor cells. Moreover, we propose that subcellular localization of Ccnd1 is an interesting guideline to measure cancer outcome.


Scalp metastasis as the first sign of small-cell lung cancer: management and literature review.
Cutaneous metastasis from primary visceral malignancy is a relatively uncommon clinical entity, with a reported incidence ranging from 0.22% to 10% among various series. However, the presence of cutaneous metastasis as the first sign of a clinically silent visceral cancer is exceedingly rare. We describe here a case of an asymptomatic male patient who presented with a solitary scalp metastasis as the initial manifestation of an underlying small-cell lung cancer. Diagnostic evaluation revealed advanced disease. We conclude that the possibility of metastatic skin disease should always be considered in the differential diagnosis in patients with a history of smoking or lung cancer presenting with cutaneous nodules. Physicians should be aware of this rare clinical entity, and appropriate investigation should be arranged for early diagnosis and initiation of the appropriate treatment. The prognosis for most patients remains poor.


Representation of therapy-related myelodysplastic syndrome in clinical trials over the past 20 years.
Therapy-related myelodysplastic syndrome (t-MDS), defined as MDS occurring after previous exposure to chemotherapy or radiotherapy, constitutes 10% to 20% of all MDS diagnoses. t-MDS patients tend to have higher-risk disease and worse outcomes than de novo MDS patients and are often excluded from therapeutic clinical trials. To explore this further, we extracted clinical trials across all status types registered on ClinicalTrials.gov from 1999 to 2018 studying untreated MDS patients. Using these specific search criteria, we analyzed 317 therapeutic MDS trials based on study status, therapeutic indication, eligibility criteria, and sponsor type to examine if these factors influenced t-MDS patient inclusion. Only 18 studies (5.7%) accrued 231 t-MDS patients in total, representing 3.2% of the total accrued MDS trial patient population. Fewer t-MDS patients were accrued in therapeutic trials sponsored by pharmaceutical sponsors vs nonpharmaceutical sponsors (2.8% vs 4.0%; P = .0073). This pattern of exclusion continues in actively enrolling trials; only 5 (10%) of 49 studies specifically mention the inclusion of t-MDS patients in their eligibility criteria. Our results indicate that therapeutic MDS trials seem to exclude t-MDS patients, rendering study results less applicable to this subset of MDS patients, who often have poor outcomes. Our study emphasizes the importance of the recent focus by National Cancer Institute cooperative groups and societies to broaden eligibility criteria for all patients.


The T2-shortening effect of gadolinium and the optimal conditions for maximizing the CNR for evaluating the biliary system: a phantom study.
Clear depiction of the common bile duct is important when evaluating neonatal cholestasis in order to differentiate biliary atresia from other diseases. During MR cholangiopancreatography, the T2-shortening effect of gadolinium can increase the contrast-to-noise ratio (CNR) of the bile duct and enhance its depiction. The purpose of this study was to confirm, by performing a phantom study, the T2-shortening effect of gadolinium, to evaluate the effect of different gadolinium chelates with different gadolinium concentrations and different magnetic field strengths for investigating the optimal combination of these conditions, and for identifying the maximum CNR for the evaluation of the biliary system. MR imaging using a T2-weighted single-shot fast spin echo sequence and T2 relaxometry was performed with a sponge phantom in a syringe tube. Two kinds of contrast agents (Gd-DTPA and Gd-EOB-DTPA) with different gadolinium concentrations were evaluated with 1.5T and 3T scanners. The signal intensities, the CNRs and the T2 relaxation time were analyzed. The signal intensities significantly decreased as the gadolinium concentrations increased (p < 0.001) with both contrast agents. These signal intensities were higher on a 3T (p < 0.001) scanner. The CNRs were higher on a 1.5T (p < 0.001) scanner and they showed no significant change with different gadolinium concentrations. The T2 relaxation time also showed a negative correlation with the gadolinium concentrations (p < 0.001) and the CNRs showed decrease more with Gd-EOB-DTPA (versus Gd-DTPA; p < 0.001) on a 3T scanner (versus 1.5T; p < 0.001). A T2-shortening effect of gadolinium exhibits a negative correlation with the gadolinium concentration for both the signal intensities and the T2 relaxation time. A higher CNR can be obtained with Gd-DTPA on a 1.5T MRI scanner.


[Effects of tumor necrosis factor antiserum of the course of Marburg hemorrhagic fever].
The paper provides data on the effect of tumor necrosis factor (TNF) antiserum on the course of experimental Marburg hemorrhagic fever. On day 3 of the challenge of guinea pigs with the Popp strain of Marburg virus, the infection event was confirmed by PCR. On days 4-7, the infected animals intramuscularly received a TNF-alpha antiserum. The treated animals showed a 50% survival while all control animals died. It may be assumed that a course of death due to Marburg hemorrhagic fever in shocks brought about by inflammatory cytokines. Therefore, attempts may be made to treat this infection by using the drugs that are TNF antagonists.